unassigned: The current study is aimed at exploring the effect of Shentong Zhuyu Decoction on the proliferation, migration, invasion, and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and its underlying molecular mechanism. unassigned: The type II collagen-induced arthritis (CIA) model was established. Subsequently, the RA-FLS were isolated from the CIA rat model and identified by immunohistochemistry. The viability, apoptosis, cell cycle, migration, and invasion of RA-FLS were detected by the cell counting kit 8 (CCK-8) assay, flow cytometry, wound-healing assay, and transwell invasion assay, respectively. The levels of MAPK p38, PPAR, CTGF, Bcl-2, Bax, caspase-3, IL-1, MMP-3, CDK4, and cyclin D1 were determined by qRT-PCR and western blotting, respectively. unassigned: After treatment with Shentong Zhuyu Decoction medicated serum, the OD value, migrative and invasive abilities, and the secretion of IL-1, MMP-3 were remarkably decreased in RA-FLS, while the apoptosis rate was increased. Further, results showed that Shentong Zhuyu Decoction inhibited the transition from the G1 phase to S phase. Additionally, Shentong Zhuyu Decoction significantly inhibited the expression of Bcl-2, CDK4, cyclin D1, MAPK p-p38, and CTGF, whereas elevated the levels of Bax, caspase-3, and PPAR. Importantly, the effects of Shentong Zhuyu Decoction were consistent with the trends of MAPK P38 inhibitor (SB203580) and PPAR agonist (GW1929). unassigned: Shentong Zhuyu Decoction inhibited viability, inflammatory response, migration, invasion, and transition from the G1 phase to S phase and promoted apoptosis of RA-FLS via the MAPK p38/PPAR/CTGF pathway.